Core-binding factor β interacts with Runx2 and is required for skeletal development

Carolina A. Yoshida, Tatsuya Furuichi, Takashi Fujita, Ryo Fukuyama, Naoko Kanatani, Shinji Kobayashi, Masanobu Satake, Kenji Takada, Toshihisa Komori

Research output: Contribution to journalArticlepeer-review

216 Citations (Scopus)

Abstract

Core-binding factor β (CBFβ, also called polyomavirus enhancer binding protein 2β (PEBP2B)) is associated with an inversion of chromosome 16 and is associated with acute myeloid leukemia in humans. CBFβ forms a heterodimer with RUNX1 (runt-related transcription factor 1), which has a DNA binding domain homologous to the pair-rule protein runt in Drosophila melanogaster. Both RUNX1 and CBFβ are essential for hematopoiesis. Haploinsufficiency of another runt-related protein, RUNX2 (also called CBFA1), causes cleidocranial dysplasia in humans and is essential in skeletal development by regulating osteoblast differentiation and chondrocyte maturation. Mice deficient in Cbfb (Cbfb-/-) die at midgestation, so the function of Cbfβ in skeletal development has yet to be ascertained. To investigate this issue, we rescued hematopoiesis of Cbfb-/- mice by introducing Cbfb using the Gata1 promoter. The rescued Cbfb-/- mice recapitulated fetal liver hematopoiesis in erythroid and megakaryocytic lineages and survived until birth, but showed severely delayed bone formation. Although mesenchymal cells differentiated into immature osteoblasts, intramembranous bones were poorly formed. The maturation of chondrocytes into hypertrophic cells was markedly delayed, and no endochondral bones were formed. Electrophoretic mobility shift assays and reporter assays showed that Cbfβ was necessary for the efficient DNA binding of Runx2 and for Runx2-dependent transcriptional activation. These findings indicate that Cbfβ is required for the function of Runx2 in skeletal development.

Original languageEnglish
Pages (from-to)633-638
Number of pages6
JournalNature Genetics
Volume32
Issue number4
DOIs
Publication statusPublished - 2002 Dec 1

ASJC Scopus subject areas

  • Genetics

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